Extracorporeal Treatment for Chloroquine, Hydroxychloroquine, and Quinine Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.

BACKGROUND: Although chloroquine, hydroxychloroquine, and quinine are used for a range of medical conditions, recent research suggested a potential role in treating COVID-19. The resultant increase in prescribing was accompanied by an increase in adverse events, including severe toxicity and death. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup sought to determine the effect of and indications for extracorporeal treatments in cases of poisoning with these drugs. METHODS: We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods. RESULTS: A total of 44 studies (three in vitro studies, two animal studies, 28 patient reports or patient series, and 11 pharmacokinetic studies) met inclusion criteria regarding the effect of extracorporeal treatments. Toxicokinetic or pharmacokinetic analysis was available for 61 patients (13 chloroquine, three hydroxychloroquine, and 45 quinine). Clinical data were available for analysis from 38 patients, including 12 with chloroquine toxicity, one with hydroxychloroquine toxicity, and 25 with quinine toxicity. All three drugs were classified as non-dialyzable (not amenable to clinically significant removal by extracorporeal treatments). The available data do not support using extracorporeal treatments in addition to standard care for patients severely poisoned with either chloroquine or quinine (strong recommendation, very low quality of evidence). Although hydroxychloroquine was assessed as being non-dialyzable, the clinical evidence was not sufficient to support a formal recommendation regarding the use of extracorporeal treatments for this drug. CONCLUSIONS: On the basis of our systematic review and analysis, the EXTRIP workgroup recommends against using extracorporeal methods to enhance elimination of these drugs in patients with severe chloroquine or quinine poisoning.

Toxic Optic Neuropathy From Quinine Overdose.

A 45-year-old man presented with longstanding poor vision in both eyes. His medical history was significant for a remote overdose of quinine. After the ingestion, he fell into a coma and on awakening was not able to see light out of both eyes. Several days later, his central vision began to gradually recover and continued to improve over the span of several months. Presently, he had 20/20 visual acuity in both eyes with severely constricted peripheral visual fields. There were bilateral iris transillumination defects, and both optic nerves were diffusely pale with attenuated vasculature and inner retinal thinning on ocular coherence tomography. We present a patient with the stereotypical findings and natural history of quinine toxicity, a rare and not widely known cause of toxic optic neuropathy and retinopathy.

Use of hyperbaric oxygen therapy in quinine-associated visual disturbances.

INTRODUCTION: Hyperbaric oxygen (HBO2 ) therapy is infrequently reported as a treatment for poison-induced retinal damage. We describe a case in which HBO2 therapy was used to treat suspected retinal toxicity induced by quinine. CASE REPORT: We present a case in which HBO2 was used to treat visual disturbances thought to be caused by quinine-induced retinal damage. The patient intentionally ingested undisclosed amounts of citalopram and quinine. Following a complicated hospital course, including profound shock requiring treatment with four vasopressors and a peripheral left-ventricular assist device, the patient, once extubated, reported visual abnormalities consistent with those described from quinine-induced retinal toxicity. Visual disturbances seemed to show improvement following HBO2 treatment. Several months following hospitalization visual defects continued to be present on examination. However, with corrective lenses the patient's visual acuity was normal. No adverse events were attributed to the use of HBO2. DISCUSSION: HBO2 for treatment of quinine-induced retinal damage is infrequently reported or studied. In the reported case, use of HBO2 appeared to be associated with substantial improvement in visual disturbances occurring in the setting of an overdose of quinine. The patient's improvement is remarkable, given her retinas were also jeopardized by her profound shock. Additional data are needed to understand the risks and benefits of this procedure, but due to limited treatment options for poison-induced retinal toxicity and the low likelihood for implementation of a controlled randomized trial of HBO2 in this population, the procedure may be considered in quinine-induced retinal toxicity.

An experimental treatment of ocular quinine toxicity with high-dose 9-cis Beta-carotene.

PURPOSE: To report a case of severe ocular quinine toxicity after a suicide attempt and an experimental treatment with high-dose 9-cis beta-carotene. METHODS: Interventional case report. RESULTS: A 59-year-old woman presented with acute bilateral blindness after ingesting high dose (12 g) of quinine sulphate. Her vision was no light perception in either eye, and her pupils were fixed and middilated. Because of limited vision and poor prognosis, she was treated with an experimental rescue therapy of high-dose 9-cis beta-carotene Dunaliella bardawil powder for 3 months, starting 10 days postingestion. Electroretinography measurements showed transient improvement in a-wave amplitudes. The electroretinography b-wave showed only partial transient improvement in the left eye. Overall, the patient's visual acuity improved to 20/33 in the right eye and 20/40 in the left eye, but with extremely constricted visual fields. CONCLUSION: Transient improvement in electroretinography measurements was observed under treatment with high-dose 9-cis beta-carotene in ocular quinine toxicity, although no clinical benefit was documented. More research is needed to determine its effect in patients with toxic retinal damage.

Ocular quinine toxicity in a sleepwalker.

A 55-year-old woman presented to the emergency department following an episode of severe visual impairment, headache, dizziness and confusion. The patient had been taking quinine sulfate as long-term medication for leg cramps. During an episode of sleepwalking, the patient had taken an overdose of quinine sulfate. Following a thorough investigation and assessment, a diagnosis of ocular quinine toxicity was made. We present this case and highlight the risks of quinine prescription.

Clinical toxicology in Edinburgh, two centuries of progress.

The Scottish Poisons Information Bureau was established in Edinburgh in September 1963 and shortly afterwards one of the wards of the city's Royal Infirmary was designated a Regional Poisoning Treatment Centre. Both units were soon to be brought under one roof. To mark this 50th anniversary, we review how they built upon a history dating from the early 19th century and highlight their influence on current clinical toxicological practice and the delivery of poisons information. While many centres worldwide seek to improve the care of poisoned patients, the contribution of Edinburgh over the past 50 years has been notable.

Relatively spared central multifocal electroretinogram responses in acute quinine toxicity.

A 71-year-old man was investigated with electrodiagnostic testing 4 months after a deliberate quinine overdose. Initially he was admitted to intensive care unit with visual acuity (VA) of perception of light in both eyes. VA recovered to 6/6 right eye and 6/12 left eye, though severely constricted fields were noted. Slow stimulus (base period of 83 ms) multifocal electroretinogram (ERG) showed electronegative responses outside the inner 5 degrees, with a reduced but electropositive response seen in this central area. It appears that in this case of bilaterally negative ERGs that the macula/fovea (which has a vascular supply through the choroid) is relatively spared as is seen in bilateral vascular electronegative ERGs. This may indicate that quinine toxicity to the retina may be secondary to effects similar to vascular occlusion or severe ischemia during the acute phase of quinine poisoning.

Clinical electrophysiology in quinine induced retinal toxicity.

A 43-year-old woman was evaluated 9 months after a deliberate overdose of quinine. The patient's visual acuity was 20/20, but she had lost all peripheral vision beyond approximately 30 degrees eccentricity. The multifocal electroretinography (mfERG) and optical coherence tomography are described for the first time in this condition. The mfERG shows electronegative waveforms beyond 6 degrees . The mfERG response density is reduced at all retinal locations. Optical coherence tomography shows thinning of the middle and inner retina by 25 to 35%, with preservation of the photoreceptor layer. Recent regulatory restrictions in off-label uses of quinine products should help to reduce the incidence of adverse toxic reactions.

Are one or two dangerous? Quinine and quinidine exposure in toddlers.

Quinine and quinidine have been cited as drugs that may cause significant morbidity and mortality in toddlers who ingest one or two pills. The use of both of these drugs has declined in the United States since the 1980s. A review of the literature and Poison Control data reveals that large quinine and quinidine ingestions, although rare in this country, may lead to severe toxicity and death related to cardiovascular and neurological effects in both children and adults. Although the majority of cases of quinine and quinidine toxicity in toddlers occur after ingestions of more than two pills, a single report each of severe toxicity after the equivalent of an ingestion of two pills or less by a toddler exists for both quinine and quinidine. Although the risk to the toddler exposed to one or two tablets seems to be small, triage to an Emergency Department is warranted after quinidine ingestion of any amount and after quinine ingestion that exceeds the age-appropriate therapeutic dose.

Acute confusion and blindness from quinine toxicity.

Quinine is widely used for nocturnal leg cramps, despite limited evidence of its clinical efficacy in this condition. Accidental overdose is associated with serious ocular complications and can potentially be fatal. We report the case of a 57-year-old man who presented with acute confusion and bilateral blindness after consuming approximately 7.2 g quinine sulphate along with an unknown quantity of alcohol. He was treated with general supportive measures and nitrates, with an apparent initial recovery, but visual field defects persisted. This case highlights the potential toxic effects of quinine, the dangers of its bulk prescription, and the lack of strict guidelines with regard to its prescription. We suggest that restricted prescribing for leg cramps, better patient education about the toxic nature of the drug, and clear labelling of this hazard on the dispensing bottles might lead to a reduction in the cases of quinine poisoning.

Death by quinine.

We report a case of a man with a 9.75 g ingestion of quinine. The patient presented with recurrent pulseless wide complex tachycardia for which he received sodium bicarbonate, defibrillation and overdrive mechanical pacing. Despite treatment, the patient died. Quinine is still available for the treatment of leg cramps and drug-resistant malaria. In overdose, quinine affects multiple organ systems, including vision, hearing, the cardiovascular, and renal systems. We review the current approach to quinine intoxication.

Quinine intoxications reported to the Scottish Poisons Information Bureau 1997-2002: a continuing problem.

Quinine is widely prescribed in the UK for night cramps. Its potential toxicity in overdose is well known. We have reviewed the Scottish experience of enquiries regarding quinine overdose to the poisons information service responsible for Scotland over a 6-year period. Between 1997 and 2002 there were 96 reports of suspected quinine toxicity from Scotland (population 5.2 million), 19 of which were in children. The largest quantities of drug ingested were in patients between the ages of 11 and 30. In comparison with older studies the pattern of quinine poisoning does not appear to have changed in the UK over 20 years, despite recognition that it is a toxic agent in overdose, and particularly in children.

Quinine ocular toxicity: treatment of blindness using therapy for vasospasm.

A case of ocular toxicity with vasospasm secondary to quinine poisoning is described. Therapy for vasospasm using nimodipine, hypertension, haemodilution and hypervolaemia was instituted with subsequent resolution of symptoms.

Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists.

In preparing this Position Statement, all relevant scientific literature was identified and reviewed critically by acknowledged experts using agreed criteria. Well-conducted clinical and experimental studies were given precedence over anecdotal case reports and abstracts were not usually considered. A draft Position Statement was then produced and subjected to detailed peer review by an international group of clinical toxicologists chosen by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. The Position Statement went through multiple drafts before being approved by the Boards of the two societies. The Position Statement includes a summary statement for ease of use and is supported by detailed documentation which describes the scientific evidence on which the Statement is based. Although many studies in animals and volunteers have demonstrated that multiple-dose activated charcoal increases drug elimination significantly, this therapy has not yet been shown in a controlled study in poisoned patients to reduce morbidity and mortality. Further studies are required to establish its role and the optimal dosage regimen of charcoal to be administered. Based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. With all of these drugs there are data to confirm enhanced elimination, though no controlled studies have demonstrated clinical benefit. Although volunteer studies have demonstrated that multiple-dose activated charcoal increases the elimination of amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, and sotalol, there are insufficient clinical data to support or exclude the use of this therapy. The use of multiple-dose charcoal in salicylate poisoning is controversial. One animal study and 2 of 4 volunteer studies did not demonstrate increased salicylate clearance with multiple-dose charcoal therapy. Data in poisoned patients are insufficient presently to recommend the use of multiple-dose charcoal therapy for salicylate poisoning. Multiple-dose activated charcoal did not increase the elimination of astemizole, chlorpropamide, doxepin, imipramine, meprobamate, methotrexate, phenytoin, sodium valproate, tobramycin, and vancomycin in experimental and/or clinical studies. Unless a patient has an intact or protected airway, the administration of multiple-dose activated charcoal is contraindicated. It should not be used in the presence of an intestinal obstruction. The need for concurrent administration of cathartics remains unproven and is not recommended. In particular, cathartics should not be administered to young children because of the propensity of laxatives to cause fluid and electrolyte imbalance. In conclusion, based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.